1. Field of the Invention
The present invention relates to a novel process for preparing di-tert.-butyl dicarbonate (hereinafter referred to as "DIBOC"), which is useful as a protecting agent of an amino group.
2. Description of the Related Art
DIBOC is known as an amino group-protecting agent through tert.-butoxycarbonylation of various amino groups. The tert.-butoxycarbonylation has various advantages that its reactivity is good and post-treatment is simple since by-products are substantially tert.-butyl alcohol and carbon dioxide.
Preparation processes of DIBOC are roughly classified in three groups.
The first process is disclosed in Org. Synth., 57, 45 (1975) and comprises reacting potassium tert.-butoxide with carbon dioxide in tetrahydrofuran, reacting resulting potassium tert.-butyl carbonate with phosgene to obtain ditert.-butyl tricarbonate, isolating and purifying it, and then decarboxylating it in the presence of a tertiary amine such as 1,4-diazabicyclo[2.2.2]octane as a catalyst to obtain DIBOC. In connection with this process, an improved process in which di-tert.-butyl tricarbonate is not isolated or purified (cf. Japanese Patent Kokai Publication No. 51358/1988).
The second process is disclosed in Japanese Patent Kokai Publication No. 186847/1989 and proposes the use of thionyl chloride in place of phosgene in the first process.
The third process is disclosed in Zh. Org. Khim., 15 (1), 106 (1975) and comprises reacting sodium tert.-butoxide with carbon dioxide in an aromatic hydrocarbon such as toluene, reacting a part of resulting sodium tert.-butyl carbonate with benzoyl chloride which is substituted with at least one nitro group or trichloroacetyl chloride in a mixed solvent of an aromatic hydrocarbon (e.g. toluene) and N,N-dimethylformamide to generate an active mixed acid anhydride in a reaction system, and then reacting the mixed acid anhydride with an excess amount of sodium tert.-butyl carbonate to obtain DIBOC. In a similar process disclosed in CS (Czechoslovakian Patent) 247845 and CS 247846, benzenesulfonyl chloride or p-toluenesulfonyl chloride is used in place of the acyl chloride in the above process. Further improvement of this process is disclosed in CS 257157 and CS 260076.
In the industrial production of DIBOC, each process has its own defects. That is, in the first process, highly toxic phosgene should be used, and in the second process, a yield of DIBOC is low though the problem of phosgene is solved. In the third process, the earlier report was unsatisfactory since a long reaction time, for example, 15 to 20 hours was required, while the later improvement could shorten the reaction time.
Since DIBOC is thermally unstable (cf. J. Org. Chem, 43, 2410 (1978)), isolation of DIBOC from the reaction mixture should be done by distillation under high vacuum which is not easy in the industrial scale in any of the above processes. Then, further improvement of a process for preparing DIBOC has been sought.